Treatment of a Chronic, Nonhealing Neuropathic Ulcer in a Pediatric Patient With Spinal Dysraphism: A Case Report

Studies to ascertain the safety and effectiveness of autologous platelet-rich plasma (PRP) in pediatric populations and obtain evidence to optimize protocols of care for persons with spinal dysraphism who develop neuropathic wounds are needed. A wound is defined as a disruption of the normal anatomical structure and function of the skin, and wounds that fail to proceed through an orderly and timely process to anatomical and functional integrity are considered to be chronic wounds.¹ A chronic wound is a common and challenging problem in rehabilitation settings. A neuropathic ulcer, a common cause of a chronic nonhealing wound, results because of repetitive trauma to a hyposensitive distal extremity, usually over a weight-bearing bony prominence.² Diabetes mellitus and peripheral neuropathy are common causes of neuropathic ulcer in adults, whereas spinal dysraphism is a commonly seen condition associated with neuropathic ulcers in the pediatric population.^2–4 Factors such as lack of parental care, cognitive impairment, associated deformity and adapted walking pattern, and incontinence contribute to frequent ulcerations or skin breakdown in children with spinal dysraphism.^3,4 Nutritional support, local wound care, relief from repetitive stress and shear, addressing the etiology or systemic cause, and sometimes surgical intervention are the conventional/traditional treatments in such cases.^2,3

Wound healing is a complex, dynamic process involving interactions of cytokines, growth factors, blood, and extracellular matrix.^1,5 Various local and systemic factors play an important role in the chronicity of a nonhealing wound. Repetitive stress and shear, chronic hypoxia, reperfusion injury, nutritional deficit, and growth factor abnormalities are described in literature as factors leading to chronic, nonhealing wounds.² A wide variety of advanced topical wound treatment strategies, such as hyperbaric oxygen, negative pressure wound therapy, PRP, tissue engineering, and stem cell treatment, are available.^2,6

Various in vivo and in vitro studies have documented the efficacy of autologous PRP in the production of stimulatory factors, such as transforming growth factor-beta, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular growth factor, and connective tissue growth factor, which modulate cellular proliferation, angiogenesis, and collagen and fibroblastic production.^6–9 PRP can also create a local nonspecific immune response and has been shown to exhibit antimicrobial effects against Staphylocoocus aureus and Pseudomonas aeruginosa in some in vitro studies.^7,9,10 Additionally, in chronic wounds, PRP can inhibit cytokine release from macrophages, improving tissue healing and regeneration, promoting new capillary growth, and accelerating epithelization.⁷

Treatment with PRP leads to wound healing via a continuum of events that are mutually influenced in terms of promotion and inhibition of their progression. A systematic review and meta-analysis has shown complete to partial wound healing response with PRP therapy in various skin conditions such as post-traumatic wounds, surgical wounds, neuropathic wounds, and venous ulcers.¹¹ PRP has also been used effectively in the treatment of pressure ulcers in a prospective study involving 25 patients with spinal cord injury, with 96% of patients showing improvement by the end of the fifth week of treatment.¹² 

Contraindications for the use of PRP are the presence of active infection and an inability to comply with postprocedure guidelines (eg, scheduled follow-up, weight-bearing instructions, care of dressed limb/segment). Some studies have indicated that hematologic disorders, immunosuppressive states, and coagulopathy are exclusion criteria, but these contraindications are relative and physician-dependent.¹³ Because of young cells and strong healing potential, use of PRP is less well-known in the pediatric population. A review of current clinical studies revealed ongoing use of PRP in pediatric conditions such as cleft lip, cleft palate, and closure of recurrent cleft palate fistulas.⁶ Use of autologous PRP is being considered in various clinical settings involving wound care as well as musculoskeletal and surgical conditions,^6,7 but this needs more and stronger evidence regarding formulations, techniques, and indications.^2,6,14 To the authors’ knowledge, there is no literature showing the use of PRP in neuropathic ulcer in patients with spinal dysraphism. Research is underway for use of PRP in various age groups and in various conditions, but there are no known age-based contraindications to its use topically. The current case report documents the response of a chronic, nonhealing neuropathic ulcer over the dorsum of the left foot to autologous PRP and the use of a plaster of paris cast in a child with spinal dysraphism.

Case report. An 11-year-old boy was brought by his mother as an outpatient to the Department of Physical Medicine & Rehabilitation. The patient had a bilateral foot deformity, was unable to walk, and had an ulcer on the dorsal left foot for 6 months. He was the first-born male child and was delivered at term. Spinal dysraphism (lumbosacral meningocele) was present at birth, for which the patient underwent surgery during the first week of life. The patient had missed motor milestones and developed an adapted pattern of kneeling and supported standing. The adapted walking pattern of kneeling, supported standing, and left talipes equinovarus deformity caused repetitive shear and stress leading to callosity formation over the dorsum of the left foot 6 months previously. This wound progressed slowly, with a gradual increase in depth and size. Serous discharge was noted after 3 months. Various treatment options were tried but did not yield any result. The treatment record was composed of local application of normal saline, antibacterial cream, silver colloidal gel, and hygroscopic dressing material. Off-loading was advised, but nonadherence was reported by the parents of the patient. No bracing or plaster cast application was done. Treatments such as hyperbaric oxygen therapy and negative pressure wound therapy were recommended to the family by the Plastic Surgery Department at a tertiary care hospital during prior visits. These treatments were not pursued due to costs. 

On examination in the Department of Physical Medicine & Rehabilitation, the child had age-appropriate cognition. The wound over the dorsum of the left foot was circular to oval shaped, measured 9 cm², had moderate exudation, slough on the wound bed, indurated margins, and punched-out edges. There was reduced muscle bulk in both lower limbs, along with left equinovarus (40 degrees) and right equinus (20 degrees) deformity. Manual muscle testing showed normal power in both upper limbs, hip, and knee joints, and there was no active movement (zero power) in the bilateral ankle-foot region. 

Functionally, the patient had age-appropriate hand function and independence in self-care activities. Mode of indoor ambulation was by crawling or kneeling; when outdoors, the patient was carried by his mother. The patient could climb stairs by kneeling and was able to stand with support for 2 to 3 minutes with weight-bearing on the left dorsal aspect of the foot and right metatarsal heads. Because of multiple treatment visits for the nonhealing wound, the patient was frequently absent from school. 

Results of laboratory tests showed a normal hemogram (hemoglobin, 12.1 g/dL; leukocytes, 7300/mm³; platelet count, 220 000/mm³; and normocytic normochromic erythrocytes) and normal protein levels (total proteins, 6.4 g/dL; albumin, 4.1 g/dL). A wound culture was obtained and showed no growth of microorganisms. A radiograph of the left ankle-foot showed no signs of recent or previous infection in the bone.

Repetitive stress, adapted mobility pattern, equinovarus deformity, hyposensitive extremities, difficulty in providing adequate off-loading (due to bilateral lower limb weakness and deformity), and a history of nonadherence to treatment recommendations were factors contributing to treatment difficulties. 

Measures. After discussion with the patient’s parents, it was determined that wound healing was the first goal of treatment. With the aim of restoring anatomical and functional integrity of the skin and doing so cost-effectively, autologous PRP was planned for wound healing after parental counseling was performed and written informed consent of the primary legal guardian (mother) of the child was obtained, as per the institution’s policy. Consent was also obtained for sharing relevant information and illustrations for this case report.

A double-spin method was followed to obtain the pure PRP from whole blood.^15,16 A microprocessor-based centrifuge (Bio Enterprises, Aligarh Uttar Pradesh, India) was used for preparation of PRP. Whole blood collection was done in a sterile centrifugation tube with 13.5 mL whole blood and 1.5 mL acid citrate dextrose. The first spin was carried out at 900 rotations/min for 5 minutes, and the second spin was carried out at 1500 rotations/min for 15 minutes to obtain 2 to 2.5 mL of autologous PRP (Figure 1).¹⁶ The wound was cleansed with normal saline after freshening the wound edges (excising a very thin margin of skin from the wound edge), and pure PRP was applied directly over the wound by pouring the drops using a sterile syringe and covering with paraffin gauze. A below-knee plaster of paris cast was applied over the dressing to keep it in place and to prevent contamination resulting from kneeling. Three (3) sessions of autologous PRP applications were performed on a weekly basis. Strict non–weight-bearing was advised. 

Treatment response was monitored using the Pressure Ulcer Scale for Healing (PUSH 3.0) every week.¹⁷ As per the PUSH tool, wound area (cm²), exudate amount (none, light, moderate, or heavy), and type of tissue (necrotic, slough, granulation, epithelialization, or resurfaced/closed) were documented every week (Table 1). The wound area was calculated as the product of the length (greatest dimension head to toe) times width (greatest dimension side to side) as measured by a ruler.

Figure 2 shows the treatment response with the reduction in wound size and exudate amount as well as the transition of slough to closed wound at the end of 5 weeks. The initial PUSH score of 13 was reduced to 7 after 3 sessions of PRP, showing a positive response, with the area reduced to 2.25 cm² with healthy granulation tissue and no exudate. Following epithelialization, for the next 2 weekly visits, only gauze moistened with normal saline was applied, and protective casting was done on an outpatient basis. According to the parents, the patient followed non-weight bearing strictly. Schooling was resumed with the same instructions after initiation of treatment. The PUSH score was zero at 5 weeks, showing complete wound healing. 

Neuropathic ulcer is a commonly seen complication in children with spinal dysraphism, with increasing prevalence from infancy to 10 years of age. This case report documents an expeditious healing response to the application of autologous PRP and a plaster of paris cast in an 11-year-old patient with a neuropathic ulcer secondary to mobility adaptation, ankle-foot deformity, and hyposensitive skin due to spinal dysraphism. The autologous PRP was prepared using a double-spin technique, with the first spin at 900 rotations/min for 5 minutes and the second spin at 1500 rotations/min for 15 minutes, yielding 2 to 2.5 mL of PRP that was directly applied over the wound without use of any exogenous activator.

The rationale behind using PRP was to reactivate the nonhealing wound and to make platelet-derived growth factors locally available.^6,7 In this case the child had a nonhealing wound with neuropathy due to repetitive trauma/stress leading to a neuro-ischemic ulcer with poorly vascularized tissue. Such cases need immediate relief of the abnormal and repetitive stress, protection of the wound and dressing from contamination, and separate treatment directed toward the underlying etiology.² The authors employed a holistic approach to target the underlying pathology (autologous PRP), provide relief from repetitive stress (off-loading/non–weight-bearing), and protect the wound and dressing (plaster of paris cast) in the current case.

Jo et al¹⁶ studied PRP gel optimization with varying times and centrifugation forces; they obtained significant platelet recovery with platelet concentration 3 to 5 times higher than whole blood, which is desirable for wound healing, using a double centrifugation technique. Whole blood (9 mL) was subjected to the first spin at 900 rotations/min for 5 minutes and a second spin at 1500 rotations/min for 15 minutes.¹⁶ The authors in the present study followed the same technique with 13.5 mL of whole blood.

PRP causes various local changes due to activation of platelets. This can be achieved with external agents, such as calcium chloride, as suggested in the literature and also as used by some authors in clinical prospective study.^6,7,12 Such use of an external agent is considered an exogenous activation of platelets. As a physiological phenomenon, platelet activation can be achieved when it comes in contact with tissue collagen, known as endogenous activation. The current study showed a complete wound healing response without using any external agent for platelet activation. It supports and justifies the application of PRP in soft tissue without exogenous activation because of the presence of natural activator collagen.^7,18  

Various in vitro studies have stated that the maximum amount of growth factors are released in the first hour after formation of PRP and are presynthesized; after this initial burst, platelets synthesize and secrete additional growth factor for 7 to 8 days.^7,19,20 This supports the sufficiency of weekly PRP therapy in this case. 

The authors used a plaster of paris cast as a protective dressing because it is a simple, easily available, and cost-effective option. However, there is no literature showing the use of such a protective dressing in the management of neuropathic ulcers in patients with spinal dysraphism. When treating chronic wounds or neuropathic ulcers, an appropriate and easy-to-administer tool is useful to monitor treatment response. This study shows the utility of the PUSH 3.0 tool in monitoring treatment response in the case of a neuropathic ulcer, similar to other studies involving pressure ulcer and chronic venous ulcer.^21,22

The patient in the case study presented in this article underwent regular follow-up and rehabilitation for 3 months without any recurrence of the wound. The parents and patient were counseled regarding regular inspection of hyposensitive skin and non-weight bearing until the deformity was corrected. 

The results of this case study cannot be extrapolated to other populations. The possible release of unmeasured growth factors during centrifugation, nonquantification of growth factors, and platelet concentrate were not evaluated. In addition, it is difficult to quantify the role of non–weight-bearing and PRP application in the facilitation of wound healing when used in combination. The protocol for preparation of PRP should be standardized, and large-scale trials with simplified and easily administered standardized protocols are needed to establish a uniform treatment strategy with autologous PRP for chronic wound care. 

This case study describes a protocol of care for an 11-year-old boy with spinal dysraphism and a chronic, nonhealing wound on the dorsum of the left foot. Epithelization was observed after 3 weekly applications of autologous PRP, and complete healing was seen in the subsequent 2 weeks with saline-moistened dressing, making PRP a promising alternative to conventional wound healing techniques. Information about treatment protocols for chronic wounds in this patient population as well as the safety and effectiveness of autologous PRP in pediatric patients is limited. Studies to standardize protocols for both are needed.

Dr. Joshi is a registrar (senior resident), Dr. More is an associate professor, and Dr. Mhambre is an associate professor and head of the department, Department of Physical Medicine and Rehabilitation, All Institute of Physical Medicine and Rehabilitation, Mumbai, India. Address all correspondence to: Ameya D. Joshi, Dhanwantari-1, Flat no. 8, Third Floor, JJ Hospital Campus, Mumbai (MH)- 400008, India; tel: +91-22-23735568 / +91-7045756378; email: drameyadjoshi@gmail.com.